Hormonal Contraception and Endometrial Thickness in IVF/ICSI Cycles: A Multicentre Historical Cohort Study

Mette Peters Michaelsen; Laura Cæcilie Nielsen; Michelle Poulsen; Regitze Gyldenholm Skals; Bettina Troest; Janne Gasseholm Bentzen; Jimmi Elers; Anette Vestergaard Gabrielsen; Marie Louise Grøndahl; Betina Boel Povlsen; Mikael Tang-Pedersen; Ulrik Schiøler Kesmodel

doi:10.1111/1471-0528.18295

Hormonal Contraception and Endometrial Thickness in IVF/ICSI Cycles: A Multicentre Historical Cohort Study

Michaelsen MP, Nielsen LC, Poulsen M, Skals RG, Troest B, Bentzen JG, Elers J, Gabrielsen AV, Grøndahl ML, Povlsen BB, Tang-Pedersen M, Kesmodel US

Published October 2025 BJOG: An International Journal of Obstetrics and Gynaecology

DOI 10.1111/1471-0528.18295 PMID 40665779 PMC PMC12411652

RRM Academy Synopsis

Past levonorgestrel IUD use linked to thinner lining in IVF cycles

In this Danish cohort, previous levonorgestrel intrauterine system (LNG-IUS) use was associated with a thinner endometrium in women having IVF/ICSI. The register-based study covered 12 786 women and 22 464 cycles. A lining under 7 mm appeared in about 15 out of 100 LNG-IUS cycles. It appeared in about 5 out of 100 no/other contraception cycles.

Key Findings

A lining under 7 mm appeared in 14.5% of LNG-IUS group cycles, the highest share, and in 4.8% of no/other contraception cycles, the lowest.
Relative to LNG-IUS, odds of a lining of ≥ 7 mm were higher after combined oral contraceptive pills (OR 3.53, 95% CI 1.29–9.65) and progestogen-only pills (OR 6.43, 95% CI 1.45–28.63).
Relative to LNG-IUS, no/other contraception had higher odds of a lining of ≥ 7 mm (OR 6.67, 95% CI 2.37–18.74).
After adjustment, every duration of LNG-IUS use (0–3, > 3–6, > 6–9 and > 9 years) had lower odds of a lining of ≥ 7 mm than no/other contraception.
Clinical pregnancy showed no statistically significant difference between LNG-IUS and other methods, or across LNG-IUS durations, in completed cycles that reached embryo transfer.

Interpretation

This Danish cohort study followed women having IVF/ICSI treatment and linked past LNG-IUS use with a thinner uterine lining, compared to other birth control histories. The authors note they could not adjust for genetics or past reproductive history. The findings support larger studies of how past hormonal birth control use affects the uterine lining during fertility treatment.

RRM Context

The authors describe the LNG-IUS as causing thinning of the uterine lining. Restorative Reproductive Medicine (RRM) works with the body's own cycle. Suppressive medications sit on the other side of that principle.

Our editorial summary of this paper, not the article's abstract.

Abstract

Objective

To study the association between previous use of levonorgestrel intrauterine system (LNG-IUS) and endometrial thickness (EMT) in women undergoing in vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) cycles.

Design

Multicentre historical cohort study.

Setting

Eight Danish public and private fertility clinics.

Population

12786 women aged 18-46 years contributing with an EMT measurement from 22 464 different IVF/ICSI treatment cycles between 2000 and 2021.

Methods

Exposure was previous use of LNG-IUS, combined oral contraceptive pills (OCPs), progeste-only pills (POPs), no/other contraception or combined, cumulated use of contraception when more contraceptives had been used during the inclusion period. Further, ever use of LNG-IUS was categorised into 0-3 years, > 3-6 years, > 6-9 years and > 9 years. Mixed effect logistic regression adjusted for age, BMI, smoking, educational level, total FSH dose and fertility clinic was used.

Main Outcome Measures

(S): EMT (< 7 mm ≥ 7 mm).

Results

Statistically significantly higher odds of EMT ≥ 7 mm were found for OCPs [odds ratio (OR) 3.53 (95% confidence interval (95% CI) 1.29-9.65)], POPs [OR 6.43, (95% CI 1.45-28.63)] and no/other contraception [OR 6.67, (95% CI 2.37-18.74]) relative to LNG-IUS in IVF/ICSI cycles. Further, all duration categories of ever use of LNG-IUS were associated with statistically significantly lower odds of obtaining an EMT ≥ 7 mm compared to no/other contraception.

Conclusions

In this study, previous use of LNG-IUS was associated with decreased endometrial growth in women undergoing IVF/ICSI.

Topics

Diagnostics › Endometrial Assessment › Luteal Phase Biopsy · Contraception › Long Acting Methods › Intrauterine Devices · Assisted Reproduction › Outcomes and Effectiveness › Outcomes by Diagnosis

Mette Peters Michaelsen, Laura Cæcilie Nielsen, Michelle Poulsen, Regitze Gyldenholm Skals, Bettina Troest, Janne Gasseholm Bentzen, Jimmi Elers, Anette Vestergaard Gabrielsen, Marie Louise Grøndahl, Betina Boel Povlsen, Mikael Tang-Pedersen, Ulrik Schiøler Kesmodel

M Michaelsen, L Nielsen, M Poulsen, R Skals, B Troest, J Bentzen, J Elers, A Gabrielsen, M Grøndahl, B Povlsen, M Tang-Pedersen, U Kesmodel

PMID 40665779 40665779 DOI 10.1111/1471-0528.18295 10.1111/1471-0528.18295 Michaelsen et al. 2025, Michaelsen 2025

Hormonal Contraception and Endometrial Thickness in IVF/ICSI Cycles: A Multicentre Historical Cohort Study

Past levonorgestrel IUD use linked to thinner lining in IVF cycles

Key Findings

Interpretation

RRM Context

Abstract

Topics

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